AXS-05 for Depression

Recruiting at 36 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Axsome Therapeutics, Inc.

Must not be taking: Auvelity

Disqualifiers: Other AXS-05 studies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

350 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing AXS-05, a new medication, to see if it can prevent depression from returning in people who have already improved with it. The study focuses on those with major depressive disorder and aims to maintain their balanced brain chemicals to keep them feeling better. AXS-05 (a combination of dextromethorphan and bupropion) has shown positive results in previous trials for major depressive disorder.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug AXS-05 for depression?

Research shows that AXS-05, a combination of dextromethorphan and bupropion, is effective in treating major depressive disorder. In clinical trials, patients experienced significant reductions in depression symptoms within two weeks, with high remission and response rates maintained over long-term use. ^{1 2 3 4 5}

Is AXS-05 (Dextromethorphan-Bupropion) safe for humans?

AXS-05, a combination of dextromethorphan and bupropion, is generally safe for humans but can have side effects like dizziness, nausea, headache, and insomnia. It carries a warning for increased risk of suicidal thoughts in young people and can cause seizures, especially at higher doses. ^{1 2 3 4 6}

What makes the drug AXS-05 unique for treating depression?

AXS-05 is unique because it combines dextromethorphan and bupropion to target depression through a novel mechanism, acting as an NMDA receptor antagonist and sigma-1 receptor agonist, which may offer faster relief compared to traditional antidepressants. ^{1 2 3 4 7}

Eligibility Criteria

This trial is for individuals currently diagnosed with Major Depressive Disorder (MDD) without psychotic features, experiencing a depressive episode lasting at least 4 weeks. It's not open to those who've been in AXS-05 studies before, used investigational drugs or Auvelity within the last month, or can't follow study procedures.

Inclusion Criteria

I have been experiencing a major depressive episode for at least 4 weeks.

I have been diagnosed with major depression without experiencing psychosis.

Exclusion Criteria

Medically inappropriate for study participation in the opinion of the investigator

I haven't taken any experimental drugs or used experimental devices in the last 30 days, nor have I been prescribed Auvelity.

Unable to comply with study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Treatment

Eligible subjects receive open-label AXS-05 for 10 weeks to monitor response and remission

10 weeks

Double-blind Treatment

Randomized subjects receive double-blind treatment with either AXS-05 or bupropion for 26 weeks or until relapse

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AXS-05
• Bupropion

Trial Overview The study tests if AXS-05 is better than Bupropion at preventing relapse of depression in people whose symptoms improved after taking AXS-05. Participants are randomly assigned to either drug and won't know which one they're getting during the trial.

Participant Groups

Group I: AXS-05 Experimental Treatment 1 Intervention

AXS-05 tablets, taken twice daily

Group II: Bupropion Active Control 1 Intervention

Bupropion tablets, taken twice daily

AXS-05 is already approved in United States for the following indications:

Approved in United States as Auvelity for:

• Major depressive disorder

Who Is Running the Clinical Trial?

Axsome Therapeutics, Inc.

Lead Sponsor

Trials

34

Recruited

11,600+

Findings from Research

Dextromethorphan/bupropion, a fixed-dose combination medication, was approved in August 2022 for treating major depressive disorder (MDD) in adults, highlighting its efficacy as a new treatment option.

The combination works by utilizing dextromethorphan as an NMDA receptor antagonist and sigma-1 receptor agonist, while bupropion enhances the bioavailability of dextromethorphan, potentially improving therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan/Bupropion: First Approval. Keam, SJ.[2022]

In a phase 2 trial involving 80 patients with major depressive disorder, dextromethorphan-bupropion (AXS-05) showed a significantly greater reduction in depression symptoms compared to bupropion, with a mean change in MADRS score of -13.7 points versus -8.8 points over 6 weeks.

Dextromethorphan-bupropion also resulted in higher remission rates (46.5% vs. 16.2% at week 6) and response rates (60.5% vs. 40.5% at week 6), while being generally well tolerated with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. Tabuteau, H., Jones, A., Anderson, A., et al.[2022]

In a phase 3 trial involving 327 patients with major depressive disorder, AXS-05 (dextromethorphan-bupropion) significantly improved depressive symptoms compared to placebo, with effects noticeable as early as week 1.

The treatment led to a remission rate of 39.5% compared to 17.3% for placebo, and was generally well tolerated, with no serious side effects like weight gain or increased sexual dysfunction reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI). Iosifescu, DV., Jones, A., O'Gorman, C., et al.[2022]

Auvelity, a combination of dextromethorphan and bupropion, is approved for treating major depressive disorder in adults, but it carries a boxed warning for increased risk of suicidal thoughts and behaviors in younger patients.

Common side effects include dizziness, nausea, and headache, with a risk of seizures at higher doses, highlighting the importance of careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Combination Drug for Depression. Aschenbrenner, DS.[2023]

Dextromethorphan-bupropion (Auvelity) is an FDA-approved treatment for major depressive disorder that has shown significant efficacy in reducing depression scores in phase 3 trials, with effects noticeable within two weeks.

The treatment is well-tolerated, with mild-to-moderate side effects, and long-term studies indicate high remission rates of nearly 70% and response rates over 80%, making it a promising option for fast-acting depression relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder. McCarthy, B., Bunn, H., Santalucia, M., et al.[2023]

Dextromethorphan (DXM) has been repurposed multiple times, showing its versatility as a treatment for cough, pseudobulbar affect, and now major depressive disorder when combined with bupropion.

The oral formulation of dextromethorphan and bupropion is noted for its rapid action and favorable safety profile, making it a promising option for treating major depressive disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan: From Cough Suppressant to Antidepressant. Kverno, K.[2022]

Esketamine, an NMDA antagonist administered intranasally, has been approved for treatment-resistant depression, highlighting the need for faster-acting antidepressants with different mechanisms than traditional monoamine-targeting drugs.

Dextromethorphan/bupropion is an investigational medication being developed as a potential rapid-onset treatment for depression, aiming to address the limitations of current therapies that often take weeks to show effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan/Bupropion: A Novel Oral NMDA (N-methyl-d-aspartate) Receptor Antagonist with Multimodal Activity. Stahl, SM.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Dextromethorphan/Bupropion: First Approval. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI). [2022]

4. United States pubmed.ncbi.nlm.nih.gov

New Combination Drug for Depression. [2023]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Dextromethorphan: From Cough Suppressant to Antidepressant. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Dextromethorphan/Bupropion: A Novel Oral NMDA (N-methyl-d-aspartate) Receptor Antagonist with Multimodal Activity. [2021]